Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA208723 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Pyrazinamide (PZA) is one of the first line antibiotics used for the treatment of tuberculosis (TB). we have used human monocyte and a mouse model of pulmonary TB to investigate whether treatment with PZA, in addition to its known anti-mycobacterial properties, modulate the host immune response during Mycobacterium tuberculosis (Mtb) infection.
2013-06-28 | GSE48027 | GEO
Project description:Pyrazinamide (PZA) is one of the first line antibiotics used for the treatment of tuberculosis (TB). we have used human monocyte and a mouse model of pulmonary TB to investigate whether treatment with PZA, in addition to its known anti-mycobacterial properties, modulate the host immune response during Mycobacterium tuberculosis (Mtb) infection. Mice were infected with Mtb and treatment with PZA was started at 28 days post-infection. At 42 days and 63 days post-infection, group of animals were euthanized and lung tissue was collected to isolate total RNA and used in microarray experiments. Mtb-infected, untreated animals served as controls.
2013-06-28 | E-GEOD-48027 | biostudies-arrayexpress
Project description:Infectious diseases, such as Mycobacterium tuberculosis (Mtb)-caused tuberculosis (TB), remain a global health threat exacerbated by increasing drug resistance. Host-directed therapy (HDT) is a complementing strategy for infection treatment through targeting host immune mechanisms. However, the limited understanding of the host factors and their regulatory mechanisms involved in host immune defense against infections has impeded HDT development. Here, we identify the E3 ubiquitin ligase tripartite motif-containing 27 (TRIM27) elicits host protective immunity against Mtb. Mechanistically, TRIM27 enters host cell nucleus upon Mtb infection to function as a transcription activator of transcription factor EB (TFEB). TRIM27 binds to TFEB promoter and the TFEB transcription factor cAMP responsive element binding protein 1 (CREB1), thus enhancing CREB1-TFEB promoter binding affinity and promoting CREB1 transcription activity towards TFEB, eventually leading to autophagy activation and pathogen clearance. Thus, TRIM27 contributes to host anti-Mtb immunity and targeting TRIM27/CREB1/TFEB axis serves as a promising HDT-based TB treatment.
2024-07-03 | GSE237039 | GEO
Project description:Host-pathogen interactions in Mycobacterium tuberculosis infection still remain poorly understood. We investigated the host immune response to different reference Mycobacterium tuberculosis strains in THP-1 cells. Major differences in the gene expression profiles were identified in response to infection with these strains. These findings shed new insights into the dynamic variation in tuberculosis immune response and pathogenesis. We used Affymetrix GeneChip Human Exon 1.0 ST microarrays to investigate host differential gene expression in response to different Mycobacterium tuberculosis strains.
2024-10-24 | GSE246736 | GEO
Project description:Analysis of Metfromin induced changes in the lung cells of Mycobacterium tuberculosis infected mouse at gene expression level. The hypothesis tested in the present study was whether metformin has any effect on the host immune response in Mycobacterium tuberculosis infected mice? Results provide important information on the effect of metformin on the inflammatory response and immune activation associated with mycobacterial infection. In conclusion, Metfromin normalizes the chronic inflammation associated with Mycobacterium tuberculosis infection.
2014-12-02 | GSE57275 | GEO
Project description:Paraffin-embedded lung and spleen tissues analyzed by Eksigent nanoLC-Ultra 2D System and QExactive mass spectrometer. Both lung and spleen tissues were extracted from animals at 4 different conditions (Not infected Ad libitum, Not infected Caloric restricted, Mycobacterium Tuberculosis (MTB) infected Ad libitum, Mycobacterium Tuberculosis (MTB) infected Caloric restricted). Globally, 24 and 23 runs are uploaded for lung and spleen tissues, respectively.
2020-06-10 | MSV000085573 | MassIVE
Project description:The global burden of tuberculosis (TB) is aggravated by the continuously increasing emergence of drug resistance, highlighting the need for innovative therapeutic options. The concept of host-directed therapy (HDT) as adjunctive to classical antibacterial therapy with antibiotics represents a novel and promising approach for treating TB. Here, we have focused on repurposing the clinically used anticancer drug tamoxifen, which was identified as a molecule with strong host-directed activity against intracellular Mycobacterium tuberculosis (Mtb). Using a primary human macrophage Mtb infection model, we demonstrate the potential of tamoxifen against drug-sensitive as well as drug-resistant Mtb bacteria. The therapeutic effect of tamoxifen was confirmed in an in vivo TB model based on Mycobacterium marinum infection of zebrafish larvae. Tamoxifen had no direct antimicrobial effects at the concentrations used, confirming that tamoxifen acted as an HDT drug. Furthermore, we demonstrate that the antimycobacterial effect of tamoxifen is independent of its well-known target the estrogen receptor (ER) pathway, but instead acts by modulating autophagy, in particular the lysosomal pathway. Through RNA sequencing and microscopic colocalization studies, we show that tamoxifen stimulates lysosomal activation and increases the localization of mycobacteria in lysosomes both in vitro and in vivo, while inhibition of lysosomal activity during tamoxifen treatment partly restores mycobacterial survival. Thus, our work highlights the HDT potential of tamoxifen and proposes it as a repurposed molecule for the treatment of TB.
2022-11-29 | GSE178919 | GEO
Project description:Host resistance to pulmonary infection with Mycobacterium tuberculosis is mediated by IL-1alpha.
| PRJNA147155 | ENA
Project description:Autophagy is a widespread physiological process in the body, which also protects the host by degrading invading pathogens and harmful substances during pathological conditions. However, Mycobacterium tuberculosis (MTB) can affect the process of autophagy by regulating the expres-sion of microRNAs (miRNAs), allowing for immune evasion. In this study, we constructed a model of a strong virulent strain (H37Rv) infection in human macrophage cell line. Following H37Rv infection, we screened 14 differentially expressed miRNAs by RNA-seq and bioinformatics. We predicted and demonstrated that miR-30c-1-3p inhibits autophagy and promotes macrophage survival by targeting ATG4B and ATG9B during the infection process.Additionally, the intervention of miR-30c-1-3p mimics resulted in an increased bacterial load in macrophages, suggesting that MTB achieves immune evasion by upregulating miR-30c-1-3p during infection. In conclusion, our study provides a valuable target for the development of host-directed anti-tuberculosis therapy as well as a new diagnostic marker.
2024-09-06 | GSE276178 | GEO
Project description:Control of Mycobacterium tuberculosis infection requires generation of T cells that migrate to granulomas, complex immune structures surrounding sites of bacterial replication. Here we compared the gene expression profiles of T cells in pulmonary granulomas, bronchoalveolar lavage and blood of Mtb-infected rhesus macaques to identify granuloma-enriched T cell genes. TNFRSF8/CD30 was among the top genes that was upregulated in both CD4 and CD8 granuloma T cells and independent of bacterial loads. Transcriptomic profiling of lung T cells from Mtb-infected mixed bone marrow chimeric mice showed that CD30 directly promotes CD4 T cell differentiation and effector molecule expression. Moreover, in mice CD30 expression on CD4 T cells is required for survival of Mtb infection. These results show the CD30 co-stimulatory axis is highly upregulated on granuloma T cells and is critical for the generation of protective T cell responses against Mtb infection.
2023-03-24 | GSE228113 | GEO